Objective: To assess the safety and pharmacokinetics of beclomethasone dipropionate (BDP) and its active metabolite, 17-monopropionate (17-BMP), in combination with the HIV protease inhibitors ritonavir (RTV), and darunavir/ritonavir (DRV/r). Design: Open label, prospective, randomized pharmacokinetic study in healthy volunteers. Methods: Thirty subjects received inhaled BDP 160 g twice daily (BID) from study days 1-14. On day 14, pharmacokinetic sampling for 17-BMP occurred. On day 15, subjects were randomized (1:1:1) into three groups: Group 1 (control) remained on BDP alone for 28 days; Group 2 received BDP + RTV 100 mg BID for 28 days, and Group 3 received BDP + DRV/r 600/100 mg BID for 28 days. On day 28, 17-BMP sampling was repeated and pharmacokinetic parameter values compared to those from day 14 using paired t-tests. Cortisol stimulation testing was also performed on days 14, 28, and 42 and compared within and between groups using paired t-tests and ANOVA, respectively. Results: Geometric mean ratios (day 28:day 14) (90% CI) for 17-BMP area under the concentration-time curve in Groups 1, 2, and 3, respectively, were 0.93 (0.81-1.06, p=0.27), 2.08 (1.52-2.65; p=0.006), and 0.89 (0.68-1.09; p=0.61). There were no significant reductions in serum cortisol levels within or between groups (p>0.05). Conclusions: DRV/r did not increase 17-BMP exposure while RTV alone produced a statistically significant but clinically inconsequential 2-fold increase in 17-BMP exposure; Adrenal suppression was not observed in any of the study groups. These data suggest that BDP can be safely coadministered with DRV/r and likely other RTV-boosted protease inhibitor regimens.